X-Ray Crystallographic Study of Novel Oxazole Derivatives
©2016
Textbook
37 Pages
Summary
This book is the outcome of an examination of Single Organic molecules by Single Crystal X-Ray techniques. The book is suitable for research scholars as it covers a complete analysis of novel Oxazole derivatives by Single Crystal X-Ray techniques.
Excerpt
Table Of Contents
Acknowledgements
First of all, I would like to thank Prof. Anamik Shah, *Vice-Chancellor,
Gujarat Vidyapith, Ahmedabad and Department of Chemistry, Saurashtra
University for giving me an opportunity to carry out work in his laboratory
under his guidance. He shared with me a lot of his expertise and research
insight. His wide knowledge in the field of Chemistry research and X-Ray
logical way of thinking has been of great value for me to accomplish this
chapter work. I am deeply grateful to the Institute for the trust and support that
they gave me in order to study in Single Crystal X-Ray Instrumentation, SCX-
mini model, Rigaku Company at Center of Excellence (CoE), National
Facility for Drug Discovery Complex, Department of Chemistry, Saurashtra
University, Rajkot, India. This book is dedicated to my MOTHER
"LINABEN RAMANLAL MEHARIYA" on her 50
th
Birthday. I owe my
special thanks to my beloved wife, Bhagwati Krunal Gauni Mehariya. My
special gratitude is due to my parents, my sisters and their families for their
loving support, inspiration to do my best in all matters of life. To them I
dedicate this Chapter.
This book is also dedicated to my Grand Mother-Valiben
Mehariya, Maniben Parmar, Mother in Law-Lataben Gauni and
My Masi-Madhuben Mehariya.
Krunalkumar Mehariya
5
1. Introduction
Oxazole is the aromatic compound of a wide range of heterocyclic
aromatic organic scaffolds. Structures of Oxazole mainly contain a
nitrogen atom and an oxygen atom separated by one carbon in a five
membered ring
[1]
.
Oxazole is designated as 1, 3-oxazoles to indicate the position of
heteroatoms in the ring. General structure of Oxazole (1) is given
below.
Fig. 1 General Structure of Oxazole
In the field of hetero cyclic chemistry, Oxazole and its derivatives are
wide range and consist of medicinal chemistry, natural products,
pharmaceutical chemistry and materials science.
Oxazole heterocyclic ring of the proton acidities have been
theoretically calculated and determined experimentally.
The acidity of hydrogen atom decreases in the order C(4)C(5) C(2)
carbon atom.
Oxazoles have been found to be common skeleton in several naturally
isolated compounds and have thus saved attention within the chemical
and pharmaceutical public
[3-4].
The characteristic of oxazole skeleton checked by various types of the
sophisticated analytical techniques.
The IR spectrum of oxazole shows absorbance at 1143, 1080 (ring
breathing), 1257 (C-H in plane deformation), 1536, 1499, 1327 (ring
stretch), and1045 cm
-1
.
The UV, the
max
of Oxazole depends highly on the substitution
pattern. In methanol, the parent ring system has an absorption
maximum at
max
¼ 205 nm.
Oxazole show characteristic resonances in both
1
H NMR and
13
C NMR
spectra.
The oxazole compound displays resonances (d) between 7.00 and 8.00
in the
1
H NMR spectrum, show that the aromatic region present in the
skeleton, and the presence of substituent can change the chemical shift
by up to 1 ppm
[4-5].
6
2. Oxazole-containing natural products
Several types of Oxazole-containing natural products were isolated
from various regions and importance in pharmaceuticals as well as in
synthetic organic fields.
A number of oxazole skeletons are present in a great amount of natural
products possessing a wide range of pharmacological activities. The
past few years of the marine natural products with 2, 4-concatenated
oxazoles have been isolated and synthesized.
Indolyl-oxazoles derivatives of 5-(indol-3-yl)oxazoles compounds
occurs in a variety of natural products and possess a wide range of
biological importance.
A Pimprinine (2), Indolyl-oxazoles derivatives has a wide range of
biological activities, from antibiotic and fungicidal effects to
monoamide oxidase inhibition and anti-epilepsy
[6].
Indolyl-oxazoles derivatives, Streptochlorin (3) has a wide-ranging
fungicidal activity and also an anti-proliferative agent. Streptochlorin
has isolated from the fermentation broth of a marine actinomycete
isolated from marine sediment
[7].
A series of the Breitfussins A (4a)and B (4b)are related heterocyclic
compounds, containing Indolyl-oxazole aromatic ring in the molecules
and originated from the marine organism Thelia Breitfussi
[8]
.
7
Breitfussin A and Breitfussin B is core of Indole and Oxazole ring
with interesting targets in many ways.
8
3. Chemistry
3.1 Synthesis of 5-(3-methoxy-4-(prop-2-yn-1 yloxy) phenyl)
oxazole
3.2 Preparation of 5-(3-methoxy-4-(prop-2-yn-1 yloxy) phenyl)
oxazole (6)
The 3-methoxy-4-(prop-2-yn-1-yloxy) benzaldehyde (5) (191 mg, 1.0 mmol),
TosMIC(196 mg, 1.0 mmol) and K
2
CO
3
(150 mg, 1.2 mmol) were dissolved
in methanol (2.0 mL). The solution was stirred at room temperature and reflux
for 3-4 hours at 70-75 °C, until the starting materials were not detected by
TLC. Then, the solid formed was filtered and washed with cold water (5 mL)
used without further purification.
3.3 Analytical data
5-(3-methoxy-4-(prop-2-yn-1 yloxy)phenyl) oxazole(6): White solid; Yield
90%; mp 180-182 °C; MS: m/z 230.
9
4. X-ray Structure Report
4.1 Experimental
4.1.1 Data Collection
A colorless prism crystal of C
13
H
11
NO
3
having approximate
dimensions of 0.560 × 0.480 × 0.300 mm was mounted on a glass
fiber.
All measurements were made on a Rigaku SCX mini diffractometer
using graphite monochromated Mo-K radiation.
The crystal-to-detector distance was 52.00 mm. Cell constants and an
orientation matrix for data collection corresponded to a primitive
orthorhombic cell with dimensions: a = 17.421(4) Å, b = 18.581(4) Å,
c = 6.882(2) Å, V = 2227.6(8) Å
3
.
For Z = 8 and F.W. = 229.23, the calculated density is 1.367 g/cm3.
Based on the reflection conditions of:0kl: k+l = 2n and h0l: h = 2n.
Packing considerations, a statistical analysis of intensity distribution,
and the successful solution and refinement of the structure, the space
group was determined to be:Pna21 (#33).
The data were collected at a temperature of 20 + 1 °C to a maximum
2 value of 55.0°.
A total of 540 oscillation images were collected. A sweep of data was
done using oscillations from -120.0 to 60.0° in 1.0° steps.
The exposure rate was 10.0 [sec./°]. The detector swing angle was -
30.80°.
A second sweep was performed using oscillations from -120.0 to
60.0° in 1.0° steps.
The exposure rate was 10.0 [sec./°].
The detector swing angle was -30.80°.
Another sweep was performed using oscillations from -120.0 to
60.0° in 1.0° steps.
The detector swing angle was -30.80°.
The crystal-to-detector distance was 52.00 mm.
Readout was performed in the 0.146 mm pixel mode.
4.1.2 Data Reduction
The 20901 reflections that were collected, 5047 were unique (R
int
=
0.0652), equivalent reflections were merged.
Data were collected and processed using CrystalClear (Rigaku).
The linear absorption coefficient, , for Mo-K radiation is 0.981 cm
-1
.
An empirical absorption correction was applied which resulted in
transmission factors ranging from 0.635 to 0.971.
The data were corrected for Lorentz and polarization effects.
10
4.1.3 Structure Solution and Refinement
The structure was solved by direct methods
[9]
and expanded using
Fourier techniques.
The non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were refined using the riding model.
The final cycle of full-matrix least-squares refinement
[10]
on F
2
was
based on 5047 observed reflections and 319 variable parameters and
converged (largest parameter shift was 1.19 times its esd) with
unweighted and weighted agreement factors.
The standard deviation of an observation of unit weight
[11]
was 0.96.
Unit weights were used.
The maximum and minimum peaks on the final difference Fourier map
corresponded to 0.19 and -0.15 e/Å
3
, respectively.
The absolute structure was deduced based on Flack parameter, -3(4),
using 2294 Friedel pairs
[12].
Neutral atom scattering factors were taken from Cromer and Waber
[13]
.
Anomalous dispersion effects were included in F
calc
[14]
, the values for
f' and f were those of Creagh and McAuley
[15]
.
The values for the mass attenuation coefficients are those of Creagh
and Hubbell
[16]
.
All calculations were performed using the CrystalStructure
[17]
crystallographic software package except for refinement, which was
performed using SHELXL-97
[18-19]
.
4.2 Experimental Details
4.2.1 Crystal Data
Empirical Formula
C13H11NO3
Formula Weight
229.23
Crystal Color, Habit
colorless, prism
Crystal Dimensions
0.560 ×0.480 × 0.300 mm
Crystal System
Orthorhombic
Lattice Type
Primitive
Lattice Parameters
a = 17.421(4) Å
b = 18.581(4) Å
c = 6.882(2) Å
V = 2227.6(8) Å
3
Space Group
Pna21 (#33)
Z value
8
D
calc
1.367 g/cm3
F
000
960.00
(MoK)
0.981 cm
-1
11
4.2.2 Intensity Measurements
Diffractometer
SCX mini
Radiation
MoK
( = 0.71075 Å)
graphite monochromated
Voltage, Current
50kV, 30mA
Temperature
20.0oC
Data Images
540 exposures
oscillation Range
-120.0 to 60.0°
Exposure Rate
10.0 sec./°
Detector Swing Angle
-30.80°
Detector Position
52.00 mm
Pixel Size
0.146 mm
2
max
55.0°
No. of Reflections Measured
Total: 20901
Unique: 5047 (R
int
= 0.0652)
Friedel pairs: 2294
Corrections
Lorentz-polarization
Absorption
(trans. factors: 0.635 - 0.971)
4.2.3 Structure Solution and Refinement
Structure Solution
Direct Methods (SIR92)
Refinement
Full-matrix least-squares on F
2
Function Minimized
(F
o
2
- F
c
2
)
2
Least Squares Weights
= 1/ [
2
(F
o
2
) + (0.0455 . P)
2
+ 1.0896 .P]
where P = (Max(F
o
2
0) + 2F
c
2
)/3
2 max cutoff
55.0°
Anomalous Dispersion
All non-hydrogen atoms
No. Observations (All
reflections)
5047
No. Variables
319
Reflection/Parameter Ratio
15.82
Residuals: R
1
(I2.00(I))
0.0538
Residuals: R (All reflections)
0.0947
Residuals: wR2 (All
reflections)
0.1404
Goodness of Fit Indicator
0.961
Flack Parameter
(Friedel pairs = 2294)
-3(4)
Max Shift/Error in Final Cycle 1.185
Maximum peak in Final Diff.
Map
0.19 e /Å
3
Minimum peak in Final Diff.
Map
-0.15 e /Å
3
Details
- Pages
- Type of Edition
- Erstausgabe
- Year
- 2016
- ISBN (PDF)
- 9783960675839
- ISBN (Softcover)
- 9783960670834
- File size
- 3.9 MB
- Language
- English
- Publication date
- 2016 (September)
- Keywords
- X-ray Structure Report Oxazole Single Crystal X-Ray Instrumentation Hetero cyclic chemistry Molecular chemistry
